This proposal seeks support for the continued career development of the Candidate, Larry J. Young, PhD. Dr. Young is an Associate Professor in the Department of Psychiatry and Behavioral Sciences and a faculty member in the Center for Behavioral Neuroscience (CBN) at Emory University. Emory and the CBN provide an ideal environment for the continued development of the Candidate's research program. Dr. Young's work focuses on the molecular, cellular and neurobiological mechanisms underlying complex social behaviors. The long-term goal of the Candidate is to incorporate state-of-the-art technologies to understand the molecular mechanisms underlying individual variation in social behaviors. Using the highly social and monogamous prairie vole as an animal model, the Candidate's research suggests that the vasopressin receptor (V1aR) plays a critical role in modulating affiliative behaviors. Molecular studies suggest that variation in the gene encoding V1aR (avprla) contributes to individual variation in social behavior. The Aims in this proposal are designed to test four specific hypotheses. The first Aim will test the hypothesis that polymorphisms in an avprla microsatellite directly contribute to variation in V1aR distribution in the brain using a knock-in mouse approach. The second Aim uses a viral vector-based siRNA approach to directly test the hypothesis that variation in avprla expression contributes to variation in social behavior in prairie voles. Studies in the third Aim will test the hypothesis that diversity in avprla expression in the vole is a primary source of heritable variation in social behavior using a selective breeding strategy. The fourth Aim will directly test the hypothesis that polymorphisms in the human AVPR1A contribute to variation in human social cognition. Each of these Aims involves the implementation of new experimental approaches into the Candidate's research program. The Career Development Plan will entail collaborations with colleagues at Emory and abroad to develop the Candidate's expertise in creating knock-in mice using homologous recombination, modulating gene expression using siRNA technology, genomics and human genetic analyses. The research outlined in this proposal has important implications for understanding the etiology of the social impairments associated with Autism Spectrum Disorders (ASD). Ultimately, these findings may lead to novel therapeutic targets for the treatment of the social impairments which characterize this devastating disorder.